Neutrophil-Endothelial Cell Interaction: A Multidirectional Cross-Talk in Leukotriene Generation

Abstract

The interaction between neutrophils (PMNLs)-monocytes and endothelial cells (ECs) represents the initial event in the acute inflammatory response and in the pathogenesis of vascular diseases [1]. The vascular endothelium represents a dynamically mutable interface that may undergo phenotypic modulations to a pathophysiologically dysfunctional state, characterized by a loss of critical homeostatic mechanisms present in healthy cells (e.g. reduced NO and PGI₂ synthesis, increased expression of adhesive molecules ligands) [2]. On the other hand, it has been repeatedly demonstrated that PMNLs activation, increased adhesion to ECs and tissue accumulation aggravate ischemic tissue damage in brain and heart and leukocyte depletion may decrease tissue necrosis [3]. Both PMNLs and ECs generate an impressive repertoire of biological effectors among which lipid mediators (e.g. eicosanoids: prostaglandins (PGs) and leukotrienes (cys-LT)) have attracted considerable interest. Their generation exhibits remarkable cellular specificity; however, their formation may also occur through transfer of reactive intermediates between adjacent cells (i.e. transcellular biosynthesis) which represents a specialized mode of cell communication [4]. This process suggests that the cellular environment (i.e. cell-cell interactions) represents a fundamental control mechanism in the production of lipids that may ultimately affect vascular function [5].